Long-term treatment of SOD1 ALS with tofersen: a multicentre experience in 17 patients

Mario Sabatelli, Federica Cerri, Riccardo Zuccarino, Agata Katia Patanella, Daniela Bernardo, Giulia Bisogni, Raffaella Tanel, Valeria Sansone, Massimiliano Filosto, Serena Lattante, Francesco Martello, Paolo Niccolo' Doronzio, Salvatore Stano, Bruno Antonio Zanfini, Michela Coccia, Emanuele Maria Costantini, Andrea Lizio, Gabriele Lucioli, Alessandro Padovani, Gian Paolo MerliniAmelia Conte

Research output: Contribution to journalArticle

Abstract

Background: In Amyotrophic Lateral Sclerosis (ALS) patients with SOD1 mutation the intrathecal administration of tofersen slowed down the progression of disease in a controlled clinical study, but results were not statistically significant. Methods: In this multicentre, observational study, we evaluated a cohort of 27 ALS-SOD1 patients who were treated with tofersen, focussing on 17 patients who were followed for at least 48 weeks (median period of 84 weeks, range 48–108). We compared the clinical slopes, as measured by ALSFRS-R, MRC scale and Forced Vital Capacity, during tofersen treatment with retrospective data at 1 year prior to therapy. Cerebrospinal fluid (CSF) and serum neurofilament light chains (NFL) were measured in all patients. Results: Cumulative evaluation of the ALSFRS-R and MRC progression rates showed a statistically significant change during treatment with respect to the period prior to therapy (p = 0.023 and p = 0.007, respectively). The analysis of individual patients showed that nine of the seventeen patients substantially stabilized or slightly improved. Four patients deteriorated during treatment, while in the remaining patients the very slow course did not allow to identify significant changes. CSF and serum NFL concentration markedly decreased in the near totality of patients. Increased levels of white blood cells and proteins in the CSF were found in 60% of patients. Such alterations were clinically asymptomatic in all but two patients who showed an acute pure motor radiculitis, which responded to steroid therapy. Conclusions: Clinical findings and NFL analysis strongly suggest that tofersen may have a disease-modifying effect in a subset of SOD1-ALS patients.
Original languageEnglish
Pages (from-to)5177-5186
Number of pages10
JournalJournal of Neurology
Volume271
DOIs
Publication statusPublished - 2024

Keywords

  • Amyotrophic lateral sclerosis
  • Neurofilament light chain
  • Oligonucleotide antisense
  • Tofersen

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